Anti-malaria genes give mosquitoes an edge

Researchers are one step closer to creating a viable malaria-resistant mosquito, according to a study in this week's Proceedings of the National Academy of Sciences. The authors found that, when feeding on malaria-infected blood, transgenic mosquitoes resistant to malaria infection experienced both higher fecundity and lower mortality than normal mosquitoes.

If such a mosquito could be introduced into the wild, "you may end up with populations that are refractory to the transmission of the parasite," predicted Peter Atkinson of the University of California, Riverside, who was not involved in the study.

Previous work has shown that mosquitoes infected with the malaria parasite are less fit than uninfected mosquitoes. This observation led to the hypothesis that transgenic malaria-resistant mosquitoes may outcompete wild-type mosquitoes, said study senior author Marcelo Jacobs-Lorena of Johns Hopkins Bloomberg School of Public Health. However, other studies have shown that transgenic mosquitoes may suffer a loss in fitness that balances out any gains from malaria resistance. "It was believed that just the presence of the transgene is a detriment," Jacobs-Lorena said.

Led by Mauro T. Marrelli, also of Johns Hopkins, the researchers compared the fitness of wild-type Anopheles stephensi to that of mosquitoes expressing a peptide called SM1, which prevents the malaria parasite from invading the midgut. These transgenic mosquitoes cannot become infected with Plasmodium berghei, a malaria parasite that infects mice.

The researchers placed equal numbers of wild-type and transgenic mosquitoes in a cage and fed them Plasmodium infected mouse blood. After nine generations, transgenic mosquitoes made up about 70% of the population. Additional experiments showed that transgenic mosquitoes had both higher fecundity and lower mortality than wild-type mosquitoes when fed blood containing reproducing parasites.

"It's very nice work," Atkinson said. "Some people have always said that if we make these things transgenic, they'll just be so unfit because they're genetically altered that they'll never be of any use, [so] it's actually very encouraging news."

Previous studies have shown that a different type of malaria-resistant mosquito cannot outcompete wild-type mosquitoes. However, those transgenic mosquitoes fought the malaria parasite by upregulating the immune response, which "may impose costs on the mosquito that equal, or even outweigh, the benefits of not being infected," according to Hilary Hurd of Keele University in Staffordshire, UK, who was an author on these previous studies but was not involved in the current work. "The advantage of the SM1 peptide is that it is not part of the natural immune system and appears to inhibit infection by blocking parasite invasion rather than killing the parasite," Hurd told The Scientist in an Email.

In order to have a viable system that could be introduced into the wild, scientists will still need to come up with a genetic drive mechanism to encourage the transgene to spread among mosquito populations, Jacobs-Lorena said. Even though transgenic mosquitoes outcompete wild-types in the lab, this is probably not sufficient "to promote introduction of the gene into the wild by itself," he said. But their results suggest that "we may need not as strong a drive force as originally predicted in order to accomplish this goal."

Another important step is to replicate the findings using human malaria parasites in their natural mosquito vectors, according to Robert Sinden of Imperial College London, who was not involved in the study. "If the results are repeated under these conditions we will have reason to be optimistic for the future."

Melissa Lee Phillips
mail@the-scientist.com

Links within this article

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'http://www.pnas.org


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Peter Atkinson
http://www.facultydirectory.ucr.edu/cgi-bin/pub/public_individual.pl?faculty=86

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'http://www.the-scientist.com/pubmed/12414739

Marcelo Jacobs-Lorena
http://faculty.jhsph.edu/Default.cfm?faculty_id=659

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Hilary Hurd
http://www.keele.ac.uk/depts/aep/staff/hh.htm

Robert Sinden
http://www.bio.ic.ac.uk/research/res/sinden.htm